Combretaceae, a family of shrubs and trees found in tropical or subtropical areas, is well represented in traditional medical practices. Twenty-five species in Combretum, which is a genus in Combretaceae, are known to be used for treating Hansen's disease and cancers in Africa and India. However, only a few of them, such as Combretum micrantbum and Combretum zeyberi, have been studied. Combretum caffrum, a species of Combretum, is called Mdulu in South Africa by the Zulus, while is also known as Bushveld willow, Bushwill, or Rooiblaar elsewhere. At the end of 1970s, after widespread screening, National Cancer Institute found that the Combretum genus plants can strongly inhibit the P388 lymphocytic leukemial cell. Since the beginning of 1980s, a wide interest in studying this kind of plant has been caused. During this period, Dr. G. Robert Pettit, the director of Cancer Research Institute of Arizona State University, and his four colleagues isolated combretastatins from the African willow tree Combretum caffrum which has been used by the Zulus as herbal remedies and as paint for spears. In the Journal of Canadian Chemistry, Dr. George R. Pettit stated that the bark of the tree had anti-tumor activity. Afterward, not only many compounds having high activity are isolated and identified, but also the research on their pharmacological mechanism and modifications of their structures have been developed. (Pettit, G. R.; et al. 1) Can. J. Chem. 1987, 65, 2390-2396. 2) J. Nat. Prod. 1987, 50, 119-131. 3) Experieutia 1989, 45, 209-211.) Combretastatins are a series of compounds characterized by the structure of Z-1,2-diphenyl ethylene. Among those compounds, Combretastatin A-4 [CA-4, Combretastatin, (Z)-1-(3,4,5-trimethoxy)phenyl-2-(3′-hydroxy-4′-methoxy)phenylethylene] proves to be exceptionally strong inhibitor of tubulin polymerization, and is represented by formula XVII (Pettit, G. R., et al. J. Med. Chem. 1995, 38, 1666-1672).

Recently, CA-4 shows exciting property in shutting down tumor vasculature as a tumor vascular targeting agent. (Thorpe, P. E. Clin. Cancer Res. 2004, January 15, 10(2), 415-427. West, C. M. Price, P. Anticancer Drugs. 2004, March, 15(3), 179-187. Young, S. L.; Chaplin, D. J. Expert Opin. Investig. Drugs. 2004, September, 13(9), 1171-1182.) CA-4 developed by Oxigene Inc., USA as a new anticancer drug has entered phase III clinical trial. In 1997, T. Hatanaka, et al. in Ajinomoto Co., Japan discovered that if the 3′-hydroxyl of CA-4 was replaced by amino group and then modified as amino amide, the anticancer activity of the obtained water-soluble prodrug could be greatly improved while with much less toxicity compared to CA-4 (U.S. Pat. No. 5,674,906). At present, 3′-amino CA-4 amino amide (AVE8062) developed by Aventis Pharma Co., France has entered phase II clinical trial.
Therefore, looking for new combretastatins with higher activity is an exigent task in this field.